Impact of RNA editing on functions of the serotonin 2C receptor in vivo

SNORD115 has been proposed to promote the activity of serotonin (HTR2C) receptor via its ability to base-pair with its pre-mRNA and regulate alternative RNA splicing and/or A-to-I RNA editing. Because SNORD115 genes are deleted in most patients with the Prader-Willi syndrome (PWS), diminished HTR2C receptor activity could contribute to the impaired emotional response and/or compulsive overeating characteristic of this disease. In order to test this appealing but never demonstrated hypothesis in vivo, we created a CRISPR/Cas9-mediated Snord115 knockout mouse. Surprisingly, we uncovered only modest region-specific alterations in Htr2c RNA editing profiles while Htr2c alternative RNA splicing was unchanged. These subtle changes, whose functional relevance remains uncertain, were not accompanied by any discernible defects in anxio-depressive-like phenotypes. Energy balance and eating behaviour were also normal, even after exposure to high fat diet. Our study raises questions concerning the physiological role of SNORD115, notably its involvement in behavioural disturbance associated with PWS.

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Reassessment of the involvement of Snord115 in the serotonin 2c receptor pathway in a genetically relevant mouse model

eLife ◽

10.7554/elife.60862 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Jade Hebras ◽

Virginie Marty ◽

Jean Personnaz ◽

Pascale Mercier ◽

Nicolai Krogh ◽

...

Keyword(s):

Rna Editing ◽

High Fat Diet ◽

Rna Splicing ◽

Emotional Response ◽

Physiological Role ◽

Serotonin 2C Receptor ◽

Compulsive Overeating ◽

Functional Relevance

SNORD115 has been proposed to promote the activity of serotonin (HTR2C) receptor via its ability to base pair with its pre-mRNA and regulate alternative RNA splicing and/or A-to-I RNA editing. Because SNORD115 genes are deleted in most patients with the Prader-Willi syndrome (PWS), diminished HTR2C receptor activity could contribute to the impaired emotional response and/or compulsive overeating characteristic of this disease. In order to test this appealing but never demonstrated hypothesis in vivo, we created a CRISPR/Cas9-mediated Snord115 knockout mouse. Surprisingly, we uncovered only modest region-specific alterations in Htr2c RNA editing profiles, while Htr2c alternative RNA splicing was unchanged. These subtle changes, whose functional relevance remains uncertain, were not accompanied by any discernible defects in anxio-depressive-like phenotypes. Energy balance and eating behavior were also normal, even after exposure to high-fat diet. Our study raises questions concerning the physiological role of SNORD115, notably its involvement in behavioural disturbance associated with PWS.

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Regulation of serotonin-2C receptor G-protein coupling by RNA editing

Nature ◽

10.1038/387303a0 ◽

1997 ◽

Vol 387 (6630) ◽

pp. 303-308 ◽

Cited By ~ 683

Author(s):

Colleen M. Burns ◽

Hsin Chu ◽

Susan M. Rueter ◽

Linda K. Hutchinson ◽

Hervé Canton ◽

...

Keyword(s):

G Protein ◽

Rna Editing ◽

G Protein Coupling ◽

Protein Coupling ◽

Serotonin 2C Receptor

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Recognition of RNA Editing Sites Is Directed by Unique Proteins in Chloroplasts: Biochemical Identification of cis-Acting Elements and trans-Acting Factors Involved in RNA Editing in Tobacco and Pea Chloroplasts

Molecular and Cellular Biology ◽

10.1128/mcb.22.19.6726-6734.2002 ◽

2002 ◽

Vol 22 (19) ◽

pp. 6726-6734 ◽

Cited By ~ 71

Author(s):

Tetsuya Miyamoto ◽

Junichi Obokata ◽

Masahiro Sugiura

Keyword(s):

Rna Editing ◽

Editing Site ◽

Mrna Editing ◽

Higher Plant ◽

In Vitro System ◽

Cis Acting ◽

Biochemical Identification ◽

Editing Activity

ABSTRACT RNA editing in higher-plant chloroplasts involves C-to-U conversions at specific sites. Although in vivo analyses have been performed, little is known about the biochemical aspects of chloroplast editing reactions. Here we improved our original in vitro system and devised a procedure for preparing active chloroplast extracts not only from tobacco plants but also from pea plants. Using our tobacco in vitro system, cis-acting elements were defined for psbE and petB mRNAs. Distinct proteins were found to bind specifically to each cis-element, a 56-kDa protein to the psbE site and a 70-kDa species to the petB site. Pea chloroplasts lack the corresponding editing site in psbE since T is already present in the DNA. Parallel in vitro analyses with tobacco and pea extracts revealed that the pea plant has no editing activity for psbE mRNAs and lacks the 56-kDa protein, whereas petB mRNAs are edited and the 70-kDa protein is also present. Therefore, coevolution of an editing site and its cognate trans-factor was demonstrated biochemically in psbE mRNA editing between tobacco and pea plants.

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Wilms' Tumor Suppressor GeneWT1

Journal of the American Society of Nephrology ◽

10.1681/asn.v11suppl_2s106 ◽

2000 ◽

Vol 11 (suppl 2) ◽

pp. S106-S115 ◽

Cited By ~ 3

Author(s):

CHRISTIAN MROWKA ◽

ANDREAS SCHEDL

Keyword(s):

Tumor Suppressor ◽

Rna Editing ◽

Kidney Development ◽

Wilms Tumor ◽

Suppressor Gene ◽

Structural Features ◽

Genomic Locus ◽

Developmental Abnormalities ◽

Complex Process

Abstract.Normal development of the kidney is a highly complex process that requires precise orchestration of proliferation, differentiation, and apoptosis. In the past few years, a number of genes that regulate these processes, and hence play pivotal roles in kidney development, have been identified. The Wilms' tumor suppressor geneWT1has been shown to be one of these essential regulators of kidney development, and mutations in this gene result in the formation of tumors and developmental abnormalities such as the Denys-Drash and Frasier syndromes. A fascinating aspect of theWT1gene is the multitude of isoforms produced from its genomic locus. In this review, our current understanding of the structural features ofWT1, how they modulate the transcriptional and post-transcriptional activities of the protein, and how mutations affecting individual isoforms can lead to diseased kidneys is summarized. In addition, results from transgenic experiments, which have yielded important findings regarding the function of WT1in vivo, are discussed. Finally, data on the unusual feature of RNA editing ofWT1transcripts are presented, and the relevance of RNA editing for the normal functioning of the WT1 protein in the kidney is discussed.

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